Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects

Trojanowski, John Q.; Vandeerstichele, Hugo; Korecka, Magdalena; Clark, Christopher M.; Aisen, Paul S.; Petersen, Ronald C.; Blennow, Kaj; Soares, Holly; Simon, Adam J.; Lewczuk, Piotr; Dean, Robert A.; Siemers, Eric; Potter, William Z.; Weiner, Michael W.; Jack, Clifford R.; Jagust, William J.; Toga, Arthur W.; Lee, Virginia M.‐Y.; Shaw, Leslie M.

doi:10.1016/j.jalz.2010.03.008

Cited by 273 publications

(245 citation statements)

References 33 publications

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“…Additional challenges arise from frequent coexistence with other pathologies that may have an additive or synergistic effects (Figure 5), although their mutual impact often Neuropathology using immunohistochemistry, molecular biological and genetic methods can achieve a diagnosis or classification in up to 95%, using homogenous and harmonized definitions and standardized inter-laboratory methods, standards for the assessment of nervous system lesions, and considering exact clinical data. Interdisciplinary projects/ initiatives for the standardized assessment of clinical, neuroimaging, biomarker, and neuropathological data are currently under way [39,42,47,[311][312][313][314][315][316]. In the majority of cases except those with known genetic or metabolic backgrounds, however, pathologic examination may not be able to clarify the causes or etiology of most dementing disorders [74], while some conservative authors emphasized that autopsy examination of well-studied cases of AD and other dementias still has a critical role to play [317].…”

Section: Discussionmentioning

confidence: 99%

“…Interdisciplinary projects/ initiatives for the standardized assessment of clinical, neuroimaging, biomarker, and neuropathological data are currently under way [39,42,47,[311][312][313][314][315][316]. In the majority of cases except those with known genetic or metabolic backgrounds, however, pathologic examination may not be able to clarify the causes or etiology of most dementing disorders [74], while some conservative authors emphasized that autopsy examination of well-studied cases of AD and other dementias still has a critical role to play [317].…”

Section: Discussionmentioning

confidence: 99%

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Neuropathology of Dementia Disorders

Jellinger¹

2014

J Alzheimers Dis Parkinsonism

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IntroductionDementia, encompassing deficits in several cognitive domains that are severe enough to interfere with daily functioning [1], in the new DSM V classification is classified within the broad category of major neurocognitive disorders, proposing specific criteria for the various etiologies [2]. Previously defined as the manifestation of deteriorating brain functions over time due to cell deaths in the brain caused by neurodegeneration or any other disease [3], according to recent research dementia is not primarily caused by neuronal cell death/loss, but by dysfunction and loss of synapses [4] in AD [5] and in α-synucleinopathies [6]. Other causes include cholinergic neuronal and axonal abnormalities [7,8], as well as pre-and postsynaptic cortical cholinergic deficits also occurring in early AD [9]. These changes due to disconnection of major nervous circuitries causing default networks [10][11][12][13] have been demonstrated in vivo in early AD [14], suggesting that disease progress is transmitted by neuronal pathways [15]. A prionlike spread of misfolded protein aggregates in the pathogenesis and progression of neurodegeneration is a hot spot of discussion [16][17][18][19][20][21].Both the prevalence and incidence of dementia increase exponentially with age. In 2010, 35.6 million people worldwide lived with dementia, with around 8 million new cases every year. Numbers are expected to double or triple every 5-10 years, to 135 millions in 2050, 16 millions in Europe. In 2010, 58% of all demented people lived in low-cost countries, with their proportion anticipated to rise to 71% in 2050 [22]. According to recent data from China the incidence of dementia was 9.87/1000 person years and the median standardised mortality ratio was 1.94:1 [23]. With the disproportional growth of the elderly population, dementia has become a major public health and socio-economic problem that threatens to become the scourge of our century. The total costs for dementia were US$ 604 billion in 2010 worldwide, up to 70% for social care alone [24], total payments for AD for 2013 were expected to be $ 203 billion in USA alone, not included contributions of unpaid caregivers [25]. Neuropathology of Dementia DisordersKurt A Jellinger* Institute of Clinical Neurobiology, Kenyongasse 18, A 1070, Vienna, Austria AbstractDementia, being not a specific disease but a syndrome characterized by deficits in several cognitive domains, is a major public health and socio-economic problem of our century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Despite updated concensus criteria for the clinical diagnosis of the major neurodegenerative disorders and new biomarkers, the diagnostic accuracy ranges from 65 to 96% (for Alzheimer's disease /AD), with a sensitivity versus other dementias of around 85.4% and a specificity of up to 77.7%. Pathologic assessment, using genetic and molecular biological methods, based on homogenous definitions, harmonized interlaboratory and assessment standards, can achiev...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuropathology of Dementia Disorders

Jellinger¹

2014

J Alzheimers Dis Parkinsonism

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“…Longitudinal imaging improved the model, suggesting that a significant portion of the neurodegeneration responsible for the subjects' conversion to AD occurs after the diagnosis of MCI. Trojanowski et al (2010) proposed a model for the temporal ordering of AD biomarkers in which Aβ amyloid biomarkers are the first to become abnormal. Subsequently, changes in neurodegenerative biomarkers become apparent (CSF tau, FDG-PET, MRI), and these are followed by the onset of clinical symptoms.…”

Section: Multiple Marker Combinationsmentioning

confidence: 99%

Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer’s disease.

Fichman

Oliveira

Fernandes

2011

Psychology & Neuroscience

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Dementia, especially Alzheimer's disease, has a high prevalence in the elderly population. Therefore, identifying individuals who are at a high risk for early diagnosis is crucial to allow both pharmacological and behavioral therapeutic interventions, which in some cases can delay the progression of dementia. This paper describes neuropsychological and neurobiological markers for the early diagnosis of Alzheimer's disease and presents the main risk factors, including neuropathological, neuroanatomical, neurofunctional, genetic, and neuropsychological. The literature shows that the combination of these markers is the best method for predicting Alzheimer's disease, years before its clinical manifestation. The most prevalent neurobiological and neuropsychological risk factors include (1) senile plaques and neurofibrillary tangles in the medial temporal lobe and cortical regions, (2) low concentrations of Aβ1-42 peptide and high concentrations of total tau protein and phosphorylated tau protein in cerebrospinal fluid, (3) reduced global cerebral volume, increased ventricular volume, and atrophy in the hippocampal formation and entorhinal cortex, (4) global reductions in cerebral metabolism and perfusion in the temporoparietal junction, temporal, parietal, and frontal lobes, hippocampal formation, and posterior cingulate cortex, (5) the presence of the apolipoprotein E ε4 allele, and (6) verbal anterograde episodic long-term memory impairment and executive dysfunction. The present review discusses the evidence for markers that identify individuals who are at a high risk of developing Alzheimer's disease and the importance of longitudinal studies in this context.

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“…The use of PET and biomarkers has allowed visualizing the accumulation of amiloid-beta and tau [8][9][10][11][12]; however, despite the extreme perspectiveness of these studies, no standardized research methodology has been developed yet. Moreover, several authors note that in some cases high levels of these proteins are observed in practically healthy individuals not suffering from AD [11,12].…”

Section: Introductionmentioning

confidence: 99%

Vascular factors in Alzheimer’s disease

Maksimovich¹

2012

Health

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The vascular factor in Alzheimer's disease (AD), affecting its development and progression, is one of the most urgent problems of modern neuroangiology. The research investigates the characteristics of cerebral angioarchitectonics identified at different stages of AD. The research included 106 patients: 1) The Test Group-47 patients suffering from various stages of AD; 2) The Control Group-59 patients suffering from the most common lesions of the brain accompanied by neurodegenerative changes, the development of dementia and cognitive impairment, but not having AD. All the patients underwent: the testing of cognitive functions (MMSE), the determination of severity of dementia (CDR) and AD stages (TDR), computed tomography (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), and cerebral multi-gated angiography (MUGA). Patients with AD different stages showed the following changes in angioarchitectonics and microcirculation: Absence of pronounced atherosclerotic lesions of intracranial vessels, reduction of the capillary bed in the temporal and temporo-parietal regions, development of multiple arteriovenous shunts in the same areas, early venous discharge, abnormal expansion of venous trunks that receive blood from arteriovenous shunts, venous congestion at the border of the frontal and parietal region, increased looping of intracranial arteries. Control Group patients had no combination of the abovementioned changes. These vascular changes are specific for AD and are in fact the vascular factor of this disease; they may also be called dyscirculatory angiopathy of Alzheimer's type (DAAT). Patients suffering from other diseases that are accompanied by neurodegenerative changes in the brain, dementia and cognitive impairment do not have them.

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Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects

Cited by 273 publications

References 33 publications

Neuropathology of Dementia Disorders

Neuropathology of Dementia Disorders

Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer’s disease.

Vascular factors in Alzheimer’s disease

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